A Study on Evaluating the Safety of HST101 in Healthy Chinese Participants

A Randomized, Double-Blind, Placebo-Controlled, Single-Center Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Dose of HST101 in Healthy Chinese Study Participants With Elevated LDL-C Levels

This is a single-center, randomized, double-blind, placebo-controlled, single HST101 SC dose cohort study to evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Chinese Participants with Elevated LDL-C Levels.

Study Overview

• Status: Enrolling by invitation
• Conditions: Hypercholesterolemia; Healthy Volunteers; LDL-Cholesterol
• Intervention / Treatment: Drug: HST101

Detailed Description

The planned 30 study participants will be assigned to low- or high-dose 2 cohorts and 15 participants in each cohort will be randomized to either the HST101 group or the matching dose placebo group and will be administered in subsequent or in-parallel manner. Cohort 1: 15 study participants will receive the low dose of HST101 or placebo at a corresponding dose. Cohort 2: additional 15 study participants will receive the high dose of HST101 or placebo at a corresponding dose.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610044
      • West China Hospital of Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Men and women who are ≥18 and ≤55 years of age with elevated LDL-C Levels;
• LDL-C ≥ 2.6 mmol/L (100 mg/dL) and ≤ 4.9 mmol/L (190 mg/dL) and TG ≤ 2.83 mmol/L (250 mg/dL) who are not on a lipid-lowering therapy 30 days prior to screening;
• Body mass index (BMI) ≥18 and≤28 kg/m2

Exclusion Criteria:

• Positive blood screen for HIV antibody, Treponema pallidum antibody, HBsAg or HCV antibody;
• Clinically significant liver function test abnormalities at screening, such as AST or ALT > 2 × ULN, total bilirubin > 1.5 × ULN, or ALP > 2 × ULN based on normal values;
• CK > 3 × ULN at the screening visit, it can be retested if considered to be related to exercise;
• History of prescription drug abuse, illicit drug use or alcohol abuse;
• Use of any prescription drug, herbal and compound decoction, vitamins, minerals, and OTC drugs and nutritional supplements that alter lipid metabolism within 14 days prior to Check-in and planned use of the above drugs throughout the study;
• Prior treatment with PCSK9 inhibitors, including mAbs, siRNA products, or any Adnectin products;
• History of allergy to protein-based biologics including, but not limited to, mAbs and vaccine;
• Less than 30 days or less than 5 half-lives (drug) since the end of participation in another clinical trial (drug or device), whichever is longer;
• Use of any other biologics within 3 months prior to investigational product administration;
• Any other significant clinical diseases or psychological diseases that the investigator considers to be inappropriate for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: cohort low dose HST101; HST101 single SC administration of 150 mg or placebo;	Drug: HST101; HST101 is a novel anti-PCSK9 fusion protein; Other Names: Lerodalcibep
Experimental: Experimental: cohort high dose HST101; HST101 single SC administration of 300 mg or placebo.	Drug: HST101; HST101 is a novel anti-PCSK9 fusion protein; Other Names: Lerodalcibep

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary objective of this study is to assess the safety and tolerability of a single SC dose of HST101 in Chinese healthy adult study participants with elevated LDL-C level(International Standard Unit: mmol/L)	Safety and tolerability will be assessed by the incidence and severity of treatment emergent adverse events	57 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the PD effect of a single SC dose of HST101 on serum unbound (free) PCSK9 concentrations and serum LDL-C concentrations	Serum free PCSK9 and LDL-C will be measured at baseline and various time points over 57 days	57 days
To assess the effect of a single SC dose of HST101 on blood lipids including TC, HDL-C, VLDL-C, and TG	Serum TC,HDL-C,VLDL-C and TG（ISU:mmol/L）will be measured at baseline and various time points over 57 days to assess percent change from baseline over time	57 days
To assess the PK-PD relationship following a single SC dose of HST101	The PK-PD relationship will be measured over 57 days	57 days
To assess immunogenicity (incidence, titer, and duration of ADAs/NAbs) following a single SC dose of HST101	Measurement of ADAs/NAbs will be done at baseline and various intervals after HST101 administration	57 days
To assess the pharmacokinetic characteristics and dose proportionality relathionship of HST101 following a single SC dose	The PK parameters include Cmax, Tmax, T1/2, AUC0-t, AUCinf and others if necessary	57 days
To assess the effect of a single SC dose of HST101 on serum ApoB, Apo A1 concentrations	Serum Apo B(ISU:mg/dL) , Apo A1(ISU:mg/dL) concentrations will be measured at baseline and various time points over 57 days to assess percent change from baseline over time	57 days
To assess the effect of a single SC dose of HST101 on serum Lp(a) concentrations	Serum Lp (a)(ISU: nmol/L) concentrations will be measured at baseline and various time points over 57 days to assess percent change from baseline over time	57 days

Collaborators and Investigators

• Sponsor: Hasten Biopharmaceutical Co., Ltd.
• Collaborators: Medpace, Inc.; Wuxi Apptec Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2024
• Primary Completion (Actual): January 8, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: July 2, 2024
• First Submitted That Met QC Criteria: July 10, 2024
• First Posted (Actual): July 16, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 12, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Hypercholesterolemia
• Other Study ID Numbers: HST101-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes